title: Ethanol-induced neurodegeneration in NRSF/REST neuronal conditional knockout mice.
abstract: The transcription regulator, neuron-restrictive silencer factor (NRSF), also known as repressor element-1 silencing transcription factor (REST), plays an important role in neurogenesis and various neuronal diseases such as ischaemia, epilepsy, and Huntington's disease. In these disease processes, neuronal loss is associated with abnormal expression and/or localization of NRSF. Previous studies have demonstrated that NRSF regulates the effect of ethanol on neuronal cells in vitro, however, the role of NRSF in ethanol-induced neuronal cell death remains unclear. We generated nrsf conditional knockout mice using the Cre-loxP system to disrupt neuronal expression of nrsf and its truncated forms. At postnatal day 6, ethanol significantly increased the expression of REST4, a neuron-specific truncated form of NRSF, in the brains of wild type mice, and this effect was diminished in nrsf conditional knockout mice. The apoptotic effect of ethanol was pronounced in multiple brain regions of nrsf conditional mutant mice. These results indicate that NRSF, specifically REST4, may protect the developing brain from ethanol, and provide new evidence that NRSF can be a therapeutic target in foetal alcohol syndrome (FAS).
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.forename: M
authors.initials: M
authors.lastname: Bian
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Sheng
authors.forename: H
authors.initials: H
authors.lastname: Suo
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Fei
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D000431:Ethanol; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor